BACKGROUND: Both opioid antagonist administration and cigarette smoking acutely increase hypothalamic-pituitary-adrenal (HPA) axis activity as measured by adrenocorticotropic hormone (ACTH) and cortisol levels. However, male and female smokers may differ in their response to the opioid antagonist naltrexone, which may be partially mediated by sex differences in HPA axis function. Smokers, as a group, have frequently been shown to have HPA axis dysfunction, which may have relevance to the course and maintenance of nicotine dependence. The purpose of this study was to examine possible sex differences in HPA axis function by comparing stress-hormone response to naltrexone within healthy male and female smokers. Additionally, exploratory analyses compared the combined effects of naltrexone and cigarette smoking on hormonal responsivity between the sexes. METHOD: Thirty-eight healthy smokers (22 men) were tested in two separate morning sessions after 12h of smoking abstinence. For women, self-reports of menstrual cycle information were obtained prior to each session (date of last menstruation, cycle length, reproductive phase, etc.). Each participant received 50mg naltrexone or placebo capsule (in random order) and plasma levels of ACTH and cortisol were assessed at regular intervals for several hours. A subgroup of 12 participants underwent a similar, additional session in which they smoked a single cigarette three hours after naltrexone administration. RESULTS:Naltrexone significantly increased ACTH and cortisol levels in women, but not men (DrugxSexxTime, p<0.05). A post hoc analysis suggested that women at an estimated 'high estrogen' phase had a greater cortisol response (DrugxEstrogen level, p<0.05) than those at an estimated 'low estrogen' phase. Exploratory analyses showed that smoking a single cigarette potentiated naltrexone-induced increases in ACTH (p<0.05) and cortisol (p<0.01) in all participants. CONCLUSION: The findings support the hypothesis that women are more sensitive to opioid antagonism at the level of the HPA axis. Although further studies are needed to examine mechanisms underlying these responses, both results may have clinical implications for the use of naltrexone as a treatment for nicotine dependence. Published by Elsevier Ltd.
RCT Entities:
BACKGROUND: Both opioid antagonist administration and cigarette smoking acutely increase hypothalamic-pituitary-adrenal (HPA) axis activity as measured by adrenocorticotropic hormone (ACTH) and cortisol levels. However, male and female smokers may differ in their response to the opioid antagonist naltrexone, which may be partially mediated by sex differences in HPA axis function. Smokers, as a group, have frequently been shown to have HPA axis dysfunction, which may have relevance to the course and maintenance of nicotine dependence. The purpose of this study was to examine possible sex differences in HPA axis function by comparing stress-hormone response to naltrexone within healthy male and female smokers. Additionally, exploratory analyses compared the combined effects of naltrexone and cigarette smoking on hormonal responsivity between the sexes. METHOD: Thirty-eight healthy smokers (22 men) were tested in two separate morning sessions after 12h of smoking abstinence. For women, self-reports of menstrual cycle information were obtained prior to each session (date of last menstruation, cycle length, reproductive phase, etc.). Each participant received 50mg naltrexone or placebo capsule (in random order) and plasma levels of ACTH and cortisol were assessed at regular intervals for several hours. A subgroup of 12 participants underwent a similar, additional session in which they smoked a single cigarette three hours after naltrexone administration. RESULTS:Naltrexone significantly increased ACTH and cortisol levels in women, but not men (DrugxSexxTime, p<0.05). A post hoc analysis suggested that women at an estimated 'high estrogen' phase had a greater cortisol response (DrugxEstrogen level, p<0.05) than those at an estimated 'low estrogen' phase. Exploratory analyses showed that smoking a single cigarette potentiated naltrexone-induced increases in ACTH (p<0.05) and cortisol (p<0.01) in all participants. CONCLUSION: The findings support the hypothesis that women are more sensitive to opioid antagonism at the level of the HPA axis. Although further studies are needed to examine mechanisms underlying these responses, both results may have clinical implications for the use of naltrexone as a treatment for nicotine dependence. Published by Elsevier Ltd.
Authors: Yolanda R Smith; Christian S Stohler; Thomas E Nichols; Joshua A Bueller; Robert A Koeppe; Jon-Kar Zubieta Journal: J Neurosci Date: 2006-05-24 Impact factor: 6.167
Authors: Stephanie S O'Malley; Judith L Cooney; Suchitra Krishnan-Sarin; Joel A Dubin; Sherry A McKee; Ned L Cooney; Amy Blakeslee; Boris Meandzija; Denise Romano-Dahlgard; Ran Wu; Robert Makuch; Peter Jatlow Journal: Arch Intern Med Date: 2006-03-27
Authors: Jack H Mendelson; Michelle B Sholar; Nathalie Goletiani; Arthur J Siegel; Nancy K Mello Journal: Neuropsychopharmacology Date: 2005-09 Impact factor: 7.853
Authors: Matthew S Tryon; Kimber L Stanhope; Elissa S Epel; Ashley E Mason; Rashida Brown; Valentina Medici; Peter J Havel; Kevin D Laugero Journal: J Clin Endocrinol Metab Date: 2015-04-16 Impact factor: 5.958
Authors: Frederick M Hecht; Jennifer Daubenmier; Elissa S Epel; Ashley E Mason; Robert H Lustig; Rashida R Brown; Michael Acree; Peter Bacchetti; Patricia J Moran; Mary Dallman; Barbara Laraia; Nancy Adler Journal: Appetite Date: 2015-04-27 Impact factor: 3.868
Authors: Gary S Wand; Elise M Weerts; Hiroto Kuwabara; Dean F Wong; Xiaoqiang Xu; Mary E McCaul Journal: Addict Biol Date: 2012-01-20 Impact factor: 4.280
Authors: Amanda J Skwara; Tracy E Karwoski; R Kenneth Czambel; Robert T Rubin; Michael E Rhodes Journal: Behav Brain Res Date: 2012-06-13 Impact factor: 3.332
Authors: Jennifer Daubenmier; Robert H Lustig; Frederick M Hecht; Jean Kristeller; Josh Woolley; Tanja Adam; Mary Dallman; Elissa Epel Journal: Appetite Date: 2013-11-27 Impact factor: 3.868
Authors: Andrea C King; Dingcai Cao; Stephanie S O'Malley; Henry R Kranzler; Xiaochen Cai; Harriet deWit; Alicia K Matthews; Ryan J Stachoviak Journal: J Clin Psychopharmacol Date: 2012-10 Impact factor: 3.153